Abstract:
PURPOSE:Comparison of the dissociation kinetics of rapid-acting insulins lispro, aspart, glulisine and human insulin under physiologically relevant conditions. METHODS:Dissociation kinetics after dilution were monitored directly in terms of the average molecular mass using combined static and dynamic light scattering. Changes in tertiary structure were detected by near-UV circular dichroism. RESULTS:Glulisine forms compact hexamers in formulation even in the absence of Zn2+. Upon severe dilution, these rapidly dissociate into monomers in less than 10 s. In contrast, in formulations of lispro and aspart, the presence of Zn2+ and phenolic compounds is essential for formation of compact R6 hexamers. These slowly dissociate in times ranging from seconds to one hour depending on the concentration of phenolic additives. The disadvantage of the long dissociation times of lispro and aspart can be diminished by a rapid depletion of the concentration of phenolic additives independent of the insulin dilution. This is especially important in conditions similar to those after subcutaneous injection, where only minor dilution of the insulins occurs. CONCLUSION:Knowledge of the diverging dissociation mechanisms of lispro and aspart compared to glulisine will be helpful for optimizing formulation conditions of rapid-acting insulins.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Gast K,Schüler A,Wolff M,Thalhammer A,Berchtold H,Nagel N,Lenherr G,Hauck G,Seckler Rdoi
10.1007/s11095-017-2233-0subject
Has Abstractpub_date
2017-11-01 00:00:00pages
2270-2286issue
11eissn
0724-8741issn
1573-904Xpii
10.1007/s11095-017-2233-0journal_volume
34pub_type
杂志文章abstract::Colonic absorption of recombinant human insulin-like growth factor I (rhIGF-I) was measured in vitro using both rat and minipig colon. The permeability coefficients were 8.03 +/- 1.03 and 4.75 +/- 0.43 x 10(-8) cm sec-1 in the rat and minipig, respectively. The steady-state flux in rat colon was linearly related to th...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018999106684
更新日期:1994-02-01 00:00:00
abstract:PURPOSE:Following extracellular drug clearance, we analyzed the rate of doxorubicin efflux from the nucleus of three human leukemic cells (K562, Molt4 and CCRF-CEM) and related it to their differential sensitivity to this drug, after a short drug pulse. RESULTS:For many pulse-chase regimes, K562 cell viability was lea...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9369-2
更新日期:2007-11-01 00:00:00
abstract::The influence of varying protein and fat content in milk of New Zealand White rabbits on the milk-to-plasma drug concentration (M/P) ratio of diazepam was studied. At various time points after littering, a bolus dose (1.5 mg/kg) followed by a 26-hr infusion (1.8 mg/h) of diazepam was administered to freely moving rabb...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015809418284
更新日期:1992-10-01 00:00:00
abstract:PURPOSE:This work investigated the effect of relative humidity (RH) on bipolar electrostatic charge profiles of dry powder inhaler aerosols using the Bipolar Charge Analyzer (BOLAR). METHODS:Two commercial products, Pulmicort® (400 μg, budesonide) and Bricanyl® (500 μg, terbutaline sulfate) Turbuhaler®, were used as m...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2178-3
更新日期:2017-08-01 00:00:00
abstract::Nucleic acids are increasingly being considered for therapeutic uses, either to interfere with the function of specific nucleic acids or to bind specific proteins. Three types of nucleic acid drugs are discussed in this review: aptamers, compounds which bind specific proteins; triplex forming (antigene) compounds; whi...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1023/a:1016281324761
更新日期:1995-04-01 00:00:00
abstract::Alpha- and beta-cyclodextrins and their hydroxypropyl derivatives were converted by the reaction with chlorosulfonic acid in pyridine to the corresponding sulfates. Cyclodextrin sulfates were shown by fast-atom bombardment mass spectrometry (negative ion mode, triethanolamine matrix) to be mixtures with nearly symmetr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015854402122
更新日期:1991-09-01 00:00:00
abstract::Gene delivery vectors based on adeno-associated virus (AAV) are highly promising due to several desirable features of this parent virus, including a lack of pathogenicity, efficient infection of dividing and non-dividing cells, and sustained maintenance of the viral genome. However, several problems should be addresse...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-007-9431-0
更新日期:2008-03-01 00:00:00
abstract:PURPOSE:The combination of morphine and gabapentin seems promising for the treatment of postoperative and neuropathic pain. Despite the well characterised pharmacodynamic interaction, little is known about possible pharmacokinetic interactions. The aim of this study was to evaluate whether co-administration of the two ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-016-1988-z
更新日期:2016-11-01 00:00:00
abstract:PURPOSE:Many genetic disorders, including chondrodysplasias, and acquired disorders impair growth plate function, resulting in short and sometimes malformed bones. There are multiple endocrine and paracrine factors that promote chondrogenesis at the growth plate, which could potentially be used to treat these disorders...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1636-z
更新日期:2015-07-01 00:00:00
abstract:PURPOSE:The objective of this study was to evaluate the in vivo consequences of glycyl-glutamate coadministration on gabapentin oral absorption. METHODS:Rats were administered gabapentin (10 mg/kg plus radiotracer) by gastric gavage, in the absence and presence of dipeptides, and by intravenous administration. Serial ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9272-x
更新日期:2007-08-01 00:00:00
abstract::Nanotechnology has continuously contributed to the fast development of diagnostic and therapeutic agents. Theranostic nanomedicine has encompassed the ongoing efforts on concurrent molecular imaging of biomarkers, delivery of therapeutic agents, and monitoring of therapy response. Among these formulations, polymer-bas...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-013-1103-7
更新日期:2014-06-01 00:00:00
abstract:PURPOSE:This study addresses the effect of freezing and thawing on a therapeutic monoclonal antibody (mAb) solution and the corresponding buffer formulation. Particle formation, crystallization behaviour, morphology changes and cryo-concentration effects were studied after varying the freezing and thawing rates, buffer...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2378-5
更新日期:2018-03-19 00:00:00
abstract:PURPOSE:The purpose of this study was to assess the antifungal activity and renal and hepatic toxicity of amphotericin B (AmpB) following administration of Fungizone (FZ) and a heat-treated form of FZ (HFZ) to rats infected with Aspergillus fumigatus. METHODS:Infected rats were administered FZ and HFZ at a dosing regi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000041449.46054.b4
更新日期:2004-09-01 00:00:00
abstract:PURPOSE:Recombinant human serum albumin (rHSA), secreted by a Pichia pastoris expression system, was purified by a fast and efficient method, the essential feature of which is strong but reversible binding of the protein to Blue Sepharose. The structural characteristics, stability, and ligand-binding properties of the ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1013391001141
更新日期:2001-12-01 00:00:00
abstract:PURPOSE:Non-small cell lung cancer is the leading cause of cancer related deaths globally. Considering the side effects and diminishing chemosensitivity to chemotherapy, novel treatment approaches are sought. Hence, we aim to develop a liposomal co-delivery system of pDNA expressing shRNA against PFKFB3 (pshPFKFB3) and...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2244-x
更新日期:2017-11-01 00:00:00
abstract:PURPOSE:To better understand the nature of drug-excipient interactions we have studied the phase behavior of amorphous binary and ternary mixtures of citric acid, indomethacin and PVP, as model systems. METHODS:We have prepared amorphous mixtures by co-melting or coprecipitation from solvents, and have measured glass ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011983606606
更新日期:1998-08-01 00:00:00
abstract::Diltiazem (DTZ) is a calcium channel blocker widely used in the treatment of angina and hypertension. DTZ undergoes extensive metabolism yielding several metabolites, some of which are active like N-desmethyldiltiazem (MA), desacetyldiltiazem (M1) and N-desmethyl,desacetyldiltiazem (M2). Due to the nature of its biotr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016226601988
更新日期:1995-04-01 00:00:00
abstract::A method is described for the assay of phenobarbital N-glucosylation using UDP-D-[6-3H]glucose. The radioactive phenobarbital N-glucoside conjugates [(5R)-PBG, (5S)-PBG] formed during the incubations were resolved from each other and from uncharacterized radioactive products by semipreparative HPLC. The product ratio ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015889707922
更新日期:1992-05-01 00:00:00
abstract:PURPOSE:To investigate the impact of a change in the proportions of lipid, surfactant and co-solvent on the solubilisation capacity of self-emulsifying formulations of danazol during in vitro dispersion and digestion studies and correlation with in vivo bioavailability in beagle dogs. METHODS:Formulations from within ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9194-z
更新日期:2007-04-01 00:00:00
abstract:PURPOSE:To compare the systemic delivery of deslorelin following intratracheal administration of different deslorelin formulations. The formulations included dry powders of deslorelin, large-porous deslorelin-poly(lactide-co-glycolide) (PLGA) particles, and small conventional deslorelin-PLGA particles. Also, solution f...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000032997.96823.88
更新日期:2004-07-01 00:00:00
abstract:PURPOSE:To study epidermal and polyethylene membrane penetration and retention of the sunscreen benzophenone-3 (BP) from a range of single solvent vehicles and evaluate solvent effects on permeability parameters. METHODS:The solubility of BP was measured in a number of solvents. Penetration of BP across human epidermi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011958006973
更新日期:1998-12-01 00:00:00
abstract:PURPOSE:Cationic host defence peptides constitute a promising class of therapeutic drug leads with a wide range of therapeutic applications, including anticancer therapy, immunomodulation, and antimicrobial activity. Although potent and efficacious, systemic toxicity and low chemical stability have hampered their comme...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1658-6
更新日期:2015-08-01 00:00:00
abstract:PURPOSE:To investigate how likely two extended release formulations are to be bioequivalent when they demonstrate f2 similarity. METHOD:Dissolution profiles were simulated using the Weibull model and varying model parameters around those of a reference profile. The f2 values were calculated for the comparisons of each...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0377-x
更新日期:2011-05-01 00:00:00
abstract:PURPOSE:To compare the effectiveness of trastuzumab-modified gold nanoparticles (AuNP) labeled with 177Lu (trastuzumab-AuNP-177Lu) targeted to HER2 with non-targeted AuNP-177Lu for killing HER2-overexpressing breast cancer (BC) cells in vitro and inhibiting tumor growth in vivo following intratumoral (i.t.) injection. ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-016-2082-2
更新日期:2017-03-01 00:00:00
abstract:PURPOSE:To investigate the destruction of clinically-relevant bacteria within biofilms via the sustained release of the antibiotic tetracycline from zein-based electrospun polymeric fibrous matrices and to demonstrate the compatibility of such wound dressing matrices with human skin cells. METHODS:Zein/PCL triple laye...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1782-3
更新日期:2016-01-01 00:00:00
abstract:PURPOSE:To develop a method for drawing statistical inferences from differences between multiple experimental pair distribution function (PDF) transforms of powder X-ray diffraction (PXRD) data. METHODS:The appropriate treatment of initial PXRD error estimates using traditional error propagation algorithms was tested ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-010-0259-7
更新日期:2010-12-01 00:00:00
abstract:PURPOSE:To improve the delivery of liposomes to tumors using P-selectin glycoprotein ligand 1 (PSGL1) mediated binding to selectin molecules, which are upregulated on tumorassociated endothelium. METHODS:PSGL1 was orientated and presented on the surface of liposomes to achieve optimal selectin binding using a novel st...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0875-5
更新日期:2013-02-01 00:00:00
abstract:PURPOSE:This paper attempts to correlate the hydrophobic contribution constants (faa) of 21 amino acids in small peptides with commonly used physiochemical parameters. These faa constants can then be used to predict hydrophobicity change in peptides when any one of the amino acid residue is substituted with another. M...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016008102587
更新日期:1996-08-01 00:00:00
abstract:PURPOSE:To study the influence of cytotoxicity of macromolecules, VEGF gene expression, and vascular permeability on the enhanced permeability and retention (EPR) effect. METHODS:Mice bearing xenografts of A2780 multidrug resistant human ovarian carcinoma were treated by free doxorubicin (DOX) and N-(2-hydroxypropyl)m...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1007500412442
更新日期:2000-05-01 00:00:00
abstract:PURPOSE:The aim of this study was to develop a labile sphingosine-based liposome for intramuscular gene delivery. METHODS:Sphingosine-based liposomes were formulated in a range of solutions with phosphatidylcholine, then were associated to DNA. The physico-chemical characteristics of the sphingosine/EPC liposomes and ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1019894008885
更新日期:2002-08-01 00:00:00